tbuckley/cabot-search huggingface dataset:
A Wrinkle in TIME: How Changes in the Aging ECM Drive the Remodeling of the Tumor Immune Microenvironment
Authors: Elizabeth I. Harper, Ashani T. Weeraratna
Journal: Cancer Discovery (2023)

Cancer is an age-related disease, with the majority of patients receiving their diagnosis after the age of 60 and most mortality from cancer occurring after this age. The tumor microenvironment changes drastically with age, which in turn affects cancer progression and treatment efficacy. Age-related changes to individual components of the microenvironment have received well-deserved attention over the past few decades, but the effects of aging at the interface of two or more microenvironmental components have been vastly understudied. In this perspective, we discuss the relationship between the aging extracellular matrix and the aging immune system, how they affect the tumor microenvironment, and how these multidisciplinary studies may open avenues for new therapeutics. Cancer is a disease of aging. With a rapidly aging population, we need to better understand the age-related changes that drive tumor progression, ranging from secreted changes to biophysical and immune changes.
Multimodal Analgesia Bundle and Postoperative Opioid Use Among Patients Undergoing Colorectal Surgery
Authors: Claes Gedda, Jonas Nygren, Anna Garpenbeck, Linda Hoffström, Anders Thorell, Mattias Soop
Journal: JAMA Network Open (2023)

Importance A key objective in contemporary surgery is to reduce or eliminate the usage of opioids to minimize gastrointestinal adverse effects, fatigue, and long-term opioid dependency. Objectives To evaluate the association of the implementation of a care bundle of 3 opioid-sparing interventions with the amount of opioids consumed postoperatively among patients undergoing major abdominal surgery and to examine the respective associations of the 3 components. Design, Setting, and Participants This retrospective cohort study was performed at Ersta Hospital, an elective teaching hospital in Stockholm, Sweden. All patients undergoing major colorectal surgery between January 1, 2016, through December 31, 2019, were included. Data analysis was conducted from February 1, 2020, to May 30, 2022. Exposures A care bundle consisting of an individualized opioid regimen, regular gabapentinoids, and clonidine as a rescue analgesic was gradually introduced early in the study period. Main Outcomes and Measures Amount of in-hospital administered intravenous and oral opioids on the day of surgery and the first 5 postoperative days (morphine milligram equivalents [MME]). The association between exposure and outcome was examined using multivariable linear regression. Results Overall, 842 patients had major colorectal surgery in the study period (mean [SD] age, 64.6 [15.5] years; 421 [50%] men). Median (range) opioid usage decreased from 75 (0-796) MME in 2016 to 22 (0-362) MME in 2019 ( P &amp;amp;lt; .001), and the proportion of patients receiving 45 MME or less increased from 35% to 66% ( P &amp;amp;lt; .001). On multivariable analysis (F 5, 836 = 57.5; P &amp;amp;lt; .001), an individualized opioid strategy (β = −11.6; SE = 3.8; P = .003), the use of gabapentin (β = −39.1; SE = 4.5; P &amp;amp;lt; .001), and increasing age (β = −1.0; SE = 0.11; P &amp;amp;lt; .001) were associated with less opioid consumption, while the use of clonidine was associated with more opioid intake (β = 11.6; SE = 3.6; P = .001). Conclusions and Relevance In this cohort study of 842 patients undergoing colorectal surgery, a care bundle consisting of an individualized opioid regimen, regular gabapentin, and clonidine as a rescue analgesic was found to be associated with a significant decrease in opioids consumed postoperatively. Regular gabapentin and an individualized opioid regimen were particularly strongly associated with this decrease and should be further evaluated as components of multimodal, opioid-free postoperative analgesia.
Needling Point Location Used in Sham Acupuncture for Chronic Nonspecific Low Back Pain
Authors: Boram Lee, Chan-Young Kwon, Hye Won Lee, Arya Nielsen, L. Susan Wieland, Tae-Hun Kim, Stephen Birch, Terje Alraek, Myeong Soo Lee
Journal: JAMA Network Open (2023)

When sham acupuncture is set as a control in evaluating acupuncture, the sham needling technique is usually different from acupuncture. However, the sham procedure is conducted either at the same points that are used for the acupuncture group or at nonindicated points.
Measurable residual disease monitoring in patients with acute myeloid leukemia treated with lower‐intensity therapy: Roadmap from an <scp>ELN‐DAVID</scp> expert panel
Authors: Farhad Ravandi, Jacqueline Cloos, Francesco Buccisano, Richard Dillon, Konstanze Döhner, Sylvie D. Freeman, Christopher S. Hourigan, Gerrit J. Ossenkoppele, Gail J. Roboz, Marion Subklewe, Christian Thiede, Isabell Arnhardt, Peter J. M. Valk, Adriano Venditti, Andrew H. Wei, Roland B. Walter, Michael Heuser
Journal: American Journal of Hematology (2023)

Abstract With the availability of effective targeted agents, significant changes have occurred in the management of patients with acute myeloid leukemia (AML) over the past several years, particularly for those considered unfit for intensive chemotherapy. While testing for measurable residual disease (MRD) is now routinely performed in patients treated with intensive chemotherapy to refine prognosis and, possibly, inform treatment decision‐making, its value in the context of lower‐intensity regimens is unclear. As such regimens have gained in popularity and can be associated with higher response rates, the need to better define the role of MRD assessment and the appropriate time points and assays used for this purpose has increased. This report outlines a roadmap for MRD testing in patients with AML treated with lower‐intensity regimens. Experts from the European LeukemiaNet (ELN)–DAVID AML MRD working group reviewed all available data to propose a framework for MRD testing in future trials and clinical practice. A Delphi poll served to optimize consensus. Establishment of uniform standards for MRD assessments in lower‐intensity regimens used in treating patients with AML is clinically relevant and important for optimizing testing and, ultimately, improving treatment outcomes of these patients.
Cost-Effectiveness of Vericiguat in Patients With Heart Failure With Reduced Ejection Fraction: The VICTORIA Randomized Clinical Trial
Authors: Derek S. Chew, Yanhong Li, Robert Bigelow, Patricia A. Cowper, Kevin J. Anstrom, Melanie R. Daniels, Linda Davidson-Ray, Adrian F. Hernandez, Christopher M. O’Connor, Paul W. Armstrong, Daniel B. Mark
Journal: Circulation (2023)

The VICTORIA trial (Vericiguat Global Study in Subjects With Heart Failure With Reduced Ejection Fraction) demonstrated that, in patients with high-risk heart failure, vericiguat reduced the primary composite outcome of cardiovascular death or heart failure hospitalization relative to placebo. The hazard ratio for all-cause mortality was 0.95 (95% CI, 0.84-1.07). In a prespecified analysis, treatment effects varied substantially as a function of baseline NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels, with survival benefit for vericiguat in the lower NT-proBNP quartiles (hazard ratio, 0.82 [95% CI, 0.69-0.97]) and no benefit in the highest NT-proBNP quartile (hazard ratio, 1.14 [95% CI, 0.95-1.38]). An economic analysis was a major secondary objective of the VICTORIA research program.Medical resource use data were collected for all VICTORIA patients (N=5050). Costs were estimated by applying externally derived US cost weights to resource use counts. Life expectancy was projected from patient-level empirical trial survival results with the use of age-based survival modeling methods. Quality-of-life adjustments were based on prospectively collected EQ-5D-based utilities. The primary outcome was the incremental cost-effectiveness ratio, comparing vericiguat with placebo, assessed from the US health care sector perspective over a lifetime horizon. Cost-effectiveness was estimated using the total VICTORIA cohort, both with and without interaction between treatment and baseline NT-proBNP.Life expectancy modeling results varied according to whether the observed heterogeneity of treatment effect by baseline NT-proBNP values was incorporated into the modeling. Including the interaction term, the vericiguat arm had an estimated quality-adjusted life expectancy of 4.56 quality-adjusted life-years (QALYs) compared with 4.13 QALYs for placebo (incremental discounted QALY, 0.43). Without the treatment heterogeneity/interaction term, vericiguat had 4.50 QALYs compared with 4.33 QALYs for placebo (incremental discounted QALY, 0.17). Incremental discounted costs (vericiguat minus placebo) were $28 546 with the treatment interaction and $20 948 without it. Corresponding incremental cost-effectiveness ratios were $66 509 per QALY allowing for treatment heterogeneity and $124 512 without heterogeneity.Vericiguat use in the VICTORIA trial met criteria for intermediate value, but the incremental cost-effectiveness ratio estimates were sensitive to whether the analysis accounted for observed NT-proBNP treatment effect heterogeneity. The cost-effectiveness of vericiguat was driven by the projected incremental life expectancy among patients in the lowest 3 quartiles of NT-proBNP.URL: https://www.gov; Unique identifier: NCT02861534.
Validation of co–Symptom Screening in Pediatrics Tool: a novel dyadic approach to symptom screening in pediatric patients receiving cancer treatment
Authors: Deborah Tomlinson, L Lee Dupuis, David Dix, Nicole Crellin-Parsons, Sadie Cook, Ketan Kulkarni, Tal Schechter, George A Tomlinson, Lillian Sung
Journal: JNCI Journal of the National Cancer Institute (2023)

Abstract Background Co-Symptom Screening in Pediatrics Tool (co-SSPedi) is a dyadic (child-guardian) approach to symptom assessment. Objectives were to evaluate the reliability and validity of co-SSPedi for pediatric patients receiving cancer treatments. Methods This multicenter study included dyads of patients aged 4-18 years of age with cancer or undergoing hematopoietic cell transplant and their guardians. Two groups were enrolled. The more symptomatic group included those receiving active treatment for cancer or undergoing hematopoietic cell transplant where patients were in hospital or clinic for 4 consecutive days. The less symptomatic group included those receiving maintenance therapy for acute lymphoblastic leukemia or who had completed cancer treatments. At baseline, all dyads completed co-SSPedi, and guardians completed measures of mucositis, nausea, pain, quality of life, and overall symptoms. In the more symptomatic group, dyads completed co-SSPedi and a global symptom change scale on day 4. Results There were 501 dyads included: 301 in the more symptomatic group and 200 in the less symptomatic group. Median time to complete co-SSPedi was less than 3 minutes in both groups. Test-retest reliability intraclass correlation coefficient was 0.85 (95% confidence interval [CI] = 0.77 to 0.90). For internal consistency, total co-SSPedi Cronbach alpha was 0.81 (95% CI = 0.78 to 0.83). For known groups validation, mean difference in total co-SSPedi scores between the more symptomatic and less symptomatic groups was 7.8 (95% CI = 6.7 to 8.8; P &amp;lt; .0001). For convergent validation and responsiveness, all hypothesized relationships were demonstrated. Conclusions Co-SSPedi is a novel approach to dyadic symptom assessment that is reliable, valid, and responsive in pediatric patients aged 4-18 years.
Error in Key Points
Authors: Thomas Santo
Journal: JAMA Psychiatry (2023)

Brooke S. G. Molina, PhD; Traci M. Kennedy, PhD; Andrea L. Howard, PhD; James M. Swanson, PhD; L. Eugene Arnold, MD; John T. Mitchell, PhD; Annamarie Stehli, MPH; Edward H. Kennedy, PhD; Jeffery N. Epstein, PhD; Lily T. Hechtman, MD; Stephen P. Hinshaw, PhD; Benedetto Vitiello, MD
Combination of BAL and Computed Tomography Differentiates Progressive and Non-progressive Fibrotic Lung Diseases
Authors: Joseph L. Barnett, Toby M. Maher, Jennifer K. Quint, Alex Adamson, Zhe Wu, David J. F. Smith, Bhavin Rawal, Arjun Nair, Simon L. F. Walsh, Sujal R. Desai, Peter M. George, Maria Kokosi, Gisli Jenkins, Vasilis Kouranos, Elisabetta A. Renzoni, Alex Rice, Andrew G. Nicholson, Felix Chua, Athol U. Wells, Philip L. Molyneaux, Anand Devaraj
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

Rationale: Identifying patients with pulmonary fibrosis (PF) at risk of progression can guide management. Objectives: To explore the utility of combining baseline BAL and computed tomography (CT) in differentiating progressive and nonprogressive PF. Methods: The derivation cohort consisted of incident cases of PF for which BAL was performed as part of a diagnostic workup. A validation cohort was prospectively recruited with identical inclusion criteria. Baseline thoracic CT scans were scored for the extent of fibrosis and usual interstitial pneumonia (UIP) pattern. The BAL lymphocyte proportion was recorded. Annualized FVC decrease of >10% or death within 1 year was used to define disease progression. Multivariable logistic regression identified the determinants of the outcome. The optimum binary thresholds (maximal Wilcoxon rank statistic) at which the extent of fibrosis on CT and the BAL lymphocyte proportion could distinguish disease progression were identified. Measurements and Main Results: BAL lymphocyte proportion, UIP pattern, and fibrosis extent were significantly and independently associated with disease progression in the derivation cohort (n = 240). Binary thresholds for increased BAL lymphocyte proportion and extensive fibrosis were identified as 25% and 20%, respectively. An increased BAL lymphocyte proportion was rare in patients with a UIP pattern (8 of 135; 5.9%) or with extensive fibrosis (7 of 144; 4.9%). In the validation cohort (n = 290), an increased BAL lymphocyte proportion was associated with a significantly lower probability of disease progression in patients with nonextensive fibrosis or a non-UIP pattern. Conclusions: BAL lymphocytosis is rare in patients with extensive fibrosis or a UIP pattern on CT. In patients without a UIP pattern or with limited fibrosis, a BAL lymphocyte proportion of ⩾25% was associated with a lower likelihood of progression.
Transcription factor ETV4 promotes the development of hepatocellular carcinoma by driving hepatic TNF‐α signaling
Authors: Dandan Qi, Min Lu, Pengfei Xu, Xinli Yao, Yongchen Chen, Lipeng Gan, Yong Li, Yahua Cui, Xiaomei Tong, Shuhong Liu, Jingmin Zhao, Ningning Liu, Xin Ye
Journal: Cancer Communications (2023)

Abstract Background Hepatic inflammation is the major risk factor of hepatocellular carcinoma (HCC). However, the underlying mechanism by which hepatic inflammation progresses to HCC is poorly understood. This study was designed to investigate the role of ETS translocation variant 4 (ETV4) in linking hepatic inflammation to HCC. Methods Quantitative real‐time PCR and immunoblotting were used to detect the expression of ETV4 in HCC tissues and cell lines. RNA sequencing and luciferase reporter assays were performed to identify the target genes of ETV4. Hepatocyte‐specific ETV4 ‐knockout ( ETV4 fl/fl, alb‐cre ) and transgenic ( ETV4 Hep‐TG ) mice and diethylnitrosamine‐carbon tetrachloride (DEN‐CCL 4 ) treatment experiments were applied to investigate the function of ETV4 in vivo . The Cancer Genome Atlas (TCGA) database mining and pathological analysis were carried out to determine the correlation of ETV4 with tumor necrosis factor‐alpha (TNF‐α) and mitogen‐activated protein kinase 11 (MAPK11). Results We revealed that ETV4 was highly expressed in HCC. High levels of ETV4 predicted a poor survival rate of HCC patients. Then we identified ETV4 as a transcription activator of TNF‐α and MAPK11. ETV4 was positively correlated with TNF‐α and MAPK11 in HCC patients. As expected, an increase in hepatic TNF‐α secretion and macrophage accumulation were observed in the livers of ETV4 Hep‐TG mice. The protein levels of TNF‐α, MAPK11, and CD68 were significantly higher in the livers of ETV4 Hep‐TG mice compared with wild type mice but lower in ETV4 fl/fl, alb‐cre mice compared with ETV4 fl/fl mice as treated with DEN‐CCL 4 , indicating that ETV4 functioned as a driver of TNF‐α/MAPK11 expression and macrophage accumulation during hepatic inflammation. Hepatocyte‐specific knockout of ETV4 significantly prevented development of DEN‐CCL 4 ‐induced HCC, while transgenic expression of ETV4 promoted growth of HCC. Conclusions ETV4 promoted hepatic inflammation and HCC by activating transcription of TNF‐α and MAPK11. Both the ETV4/TNF‐α and ETV4/MAPK11 axes represented two potential therapeutic targets for highly associated hepatic inflammation and HCC. ETV4+TNF‐α were potential prognostic markers for HCC patients.
Social Deprivation and Population Density Trajectories Before and After Psychotic Disorder Diagnosis
Authors: Yanakan Logeswaran, Jennifer Dykxhoorn, Christina Dalman, James B. Kirkbride
Journal: JAMA Psychiatry (2023)

People with psychosis are more likely to be born and live in densely populated and socioeconomically deprived environments, but it is unclear whether these associations are a cause or consequence of disorder.
Use of Abortion Services in Massachusetts After the <i>Dobbs</i> Decision Among In-State vs Out-of-State Residents
Authors: Brianna Keefe-Oates, Isabel Fulcher, Jennifer Fortin, Alisa B. Goldberg, Jarvis T. Chen, Barbara Gottlieb, Elizabeth Janiak
Journal: JAMA Network Open (2023)

This cohort study compares observed vs expected abortion counts after Dobbs in Massachusetts among in-state vs out-of-state residents.
FGFR Inhibition: Understanding and Overcoming Resistance
Authors: Abhishek Tripathi, Daneng Li, Sumanta K. Pal
Journal: Cancer Discovery (2023)

Summary: Facchinetti and colleagues provide key insights into the evolution of resistance to fibroblast growth factor receptor (FGFR) inhibitors, including the development of kinase domain mutations and activation of the PI3K–AKT signaling axis. In a separate study, Subbiah and colleagues report extensive preclinical data and initial clinical data for RLY-4008, an FGFR2-selective inhibitor that is poised to minimize toxicity and overcome resistance through greater potency and selectivity. See related article by Facchinetti et al., p. 1998 (5). See related article by Subbiah et al., p. 2012 (7).
Associations between Urinary Concentrations of Disinfection Byproducts and <i>in Vitro</i> Fertilization Outcomes: A Prospective Cohort Study in China
Authors: Yan-Ling Deng, Chong Liu, Xiao-Qiong Yuan, Qiong Luo, Yu Miao, Pan-Pan Chen, Fei-Peng Cui, Min Zhang, Jia-Yue Zeng, Tian Shi, Ting-Ting Lu, Yu-Feng Li, Wen-Qing Lu, Qiang Zeng
Journal: Environmental Health Perspectives (2023)

Experimental studies show that disinfection byproducts (DBPs) can inhibit oocyte maturation, decrease fertilization capacity, and impair embryo development, but human evidence is lacking.We aimed to evaluate the associations between exposure to drinking water DBPs and in vitro fertilization (IVF) outcomes.The study included 1,048 women undergoing assisted reproductive technology (ART) treatment between December 2018 and January 2020 from a prospective cohort study, the Tongji Reproductive and Environmental study in Wuhan, China. Exposure to DBPs was assessed by dichloroacetic acid (DCAA) and trichloroacetic acid (TCAA) in up to four urine samples, which were collected on the day of both enrollment and oocyte retrieval. Multivariable generalized linear mixed models, accounting for multiple IVF cycles per woman, were applied to evaluate the associations between urinary biomarkers of DBP exposures and IVF outcomes. Stratified analyses were used to explore the potential effect modifiers.The included 1,048 women underwent 1,136 IVF cycles, with 960 (91.6%), 84 (8.0%), and 4 (0.4%) women contributing one cycle, two cycles, and three cycles, respectively. We found that elevated quartiles of urinary DCAA and TCAA concentrations were associated with reduced numbers of total oocytes and metaphase II oocytes and that urinary DCAA concentrations with a lower proportion of best-quality embryos (all p for trends<0.05). Moreover, elevated quartiles of urinary DCAA concentrations were associated with decreased proportions of successful implantation, clinical pregnancy, and live birth (14%, 15%, and 15% decreases in adjusted means comparing the extreme quartiles, respectively; all p for trends<0.05). Stratification analyses showed that the inverse associations of urinary TCAA concentrations with multiple IVF outcomes were stronger among women ≥30 y of age (p for interactions<0.05).Exposure to drinking water DBPs was inversely associated with some IVF outcomes among women undergoing ART treatment. Further study is necessary to confirm our findings. https://doi.org/10.1289/EHP12447.
Express Delivery of Next-Generation CAR T Cells with Preserved Naive and Stemness Phenotypes for the Treatment of Aggressive Lymphomas
Authors: Michael Wang
Journal: Cancer Discovery (2023)

Summary: In this issue of Cancer Discovery, Dickinson and colleagues present clinical data from a first-in-human study of YTB323, a novel autologous CD19-directed chimeric antigen receptor T-cell therapy generated on the T-Charge platform with preserved naive state and stemness phenotypes. Treatment with YTB323 achieved high overall response rates, durable complete remissions, and good overall safety. Their cell doses are up to 25-fold lower than with tisagenlecleucel. See related article by Dickinson et al., p. 1982 (10).
Intercostal Recession and Bulging during Pendelluft Detected in Four-Dimensional Computed Tomography
Authors: Shinshu Katayama, Ken Tonai, Shono Atsuko
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

"Intercostal Recession and Bulging during Pendelluft Detected in Four-Dimensional Computed Tomography." American Journal of Respiratory and Critical Care Medicine, 208(10), pp. e41–e43
Maternal Perinatal Stress Trajectories and Negative Affect and Amygdala Development in Offspring
Authors: Mollie C. Marr, Alice M. Graham, Eric Feczko, Saara Nolvi, Elina Thomas, Darrick Sturgeon, Emma Schifsky, Jerod M. Rasmussen, John H. Gilmore, Martin Styner, Sonja Entringer, Pathik D. Wadhwa, Riikka Korja, Hasse Karlsson, Linnea Karlsson, Claudia Buss, Damien A. Fair
Journal: American Journal of Psychiatry (2023)

Maternal psychological stress during pregnancy is a common risk factor for psychiatric disorders in offspring, but little is known about how heterogeneity of stress trajectories during pregnancy affect brain systems and behavioral phenotypes in infancy. This study was designed to address this gap in knowledge.
Amid Health Misinformation, Most Trust Physicians for Truth
Authors: Emily Harris
Journal: JAMA (2023)

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